Based on the hypothesis that nitric oxide (NO) is released during exercise, the applicant has proposed to delineate the molecular mechanisms of exercise preconditioning (PC) by examining the role of NO in signal transduction. The goal of the research will be achieved by addressing five Specific Aims : (i) by establishing the role of PKCe in exercise PC; (ii) by establishing the role of the Src family of protein tyrosine kinase in exercise PC; (iii) by identifying the specific transcription factors responsible for the transcriptional upregulation of iNOS and the development of exercise PC; (iv) by establishing the role of PKCe-Src/Lck signaling pathway in the recruitment of the transcription factors responsible for exercise PC; and (v) by studying the role of each individual NOS isoform in triggering and mediating exercise PC and elucidating its post-translational modulation. The results of this study will shed new light on the mechanisms of exercise PC.